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Role of various tissues in apo(a) fragmentation and excretion of fragments by the kidney.

Abstract：

BACKGROUND:Lipoprotein(a) [Lp(a)] is an atherothrombotic plasma lipoprotein with unknown function. Little is known about the catabolism of this lipoprotein, in particular the steps related to apolipoprotein(a) [apo(a)] fragmentation and excretion by the kidney. MATERIAL AND METHODS:High plasma levels (up to 9 mg dL(-1)) of the N-terminal fragment of apo(a) were expressed in mice by adenovirus mediated gene transfer. Plasma of such N-apo(a) mice was injected into acceptor mice and the fragmentation and urinary secretion of N-apo(a) were followed by immunochemical techniques. RESULTS:Mice transduced with N-Ad expressed apo(a)-fragments with 3-11 kringle-IV (KIV) repeats. Injection of N-apo(a)-plasma from donor mice into acceptor mice resulted in fragmentation of N-apo(a)s with 3-11 KIVs yielding smaller peptides down to 2 KIVs. Secretion of N-apo(a)-fragments with 2 to maximally 6 KIVs into urine occurred as early as 2 min after injection. Immunohistochemical studies of kidney suggested filtration as a mechanism of apo(a)-fragment excretion. When N-apo(a) was incubated in vitro with various tissues from perfused mice, skeletal muscle and kidney followed by liver and spleen contributed to fragmentation. Tissues from unperfused organs, or the addition of normal mouse plasma, caused marked reduction in N-apo(a) fragmentation. EDTA, and not aprotinin or leupeptin, prevented apo(a) cleavage. CONCLUSION:Here we provide evidence that apo(a) is cleaved by metalloproteinases located on skeletal muscle, kidney and other organs. Small apo(a)-fragments up to a size of 6 KIVs are excreted into urine, yet a major portion of apo(a) fragments is removed from circulation extrarenally.

journal_name

Eur J Clin Invest

journal_title

European journal of clinical investigation

authors

Frank S,Hrzenjak A,Blaschitz A,Dohr G,Kostner GM

doi

10.1046/j.1365-2362.2001.00811.x

keywords:

subject

Has Abstract

pub_date

2001-06-01 00:00:00

pages

504-12

issue

6

eissn

0014-2972

issn

1365-2362

pii

eci811

journal_volume

31

pub_type

杂志文章

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